Impact of Family History and Germline Genetic Risk Single Nucleotide Polymorphisms on Long-Term Outcomes of Favorable-Risk Prostate Cancer

Abstract

Purpose: Family history and germline genetic risk single nucleotide polymorphisms (SNPs) have been separately shown to stratify lifetime risk of prostate cancer. Here, we evaluate the combined prognostic value of family history of prostate and other related cancers and germline risk SNPs among patients with favorable-risk prostate cancer. Materials and Methods: A total of 1367 participants from the prospective Health Professionals Follow-up Study diagnosed with low-or favorable intermediaterisk prostate cancer from 1986 to 2017 underwent genome-wide SNP genotyping. Multivariable Cox regression was used to estimate the association between family history, specific germline risk variants, and a 269 SNP polygenic risk score with prostate cancer-specific death. Results: Family history of prostate, breast, and/or pancreatic cancer was observed in 489 (36%) participants. With median follow-up from diagnosis of 14.9 years, participants with favorable-risk prostate cancer with a positive family history had a significantly higher risk of prostate cancer-specific death (HR 1.95,